Smart Designer Nanozymes for Precision Cancer Therapy: Recent Advances and Prospects.

Nanozymes are enzyme-mimicking nanomaterials that are promising for diverse biomedical applications; they enable stable, tunable, and multifunctional cancer therapies via exploiting tumor microenvironment (TME) cues to regulate reactive oxygen species (ROS) and catalytic activities locally, aided by state-of-the-art fabrication methods and artificial intelligence (AI)-assisted designs. This review summarizes recent developments in nanozyme-based cancer therapy, focusing on the underlying catalytic mechanisms, material classifications, and their multimodality integration for cancer treatment. It further examines oxidase (OXD), peroxidase (POD), catalase (CAT), and superoxide dismutase (SOD)-like nanozymes in chemodynamic (CDT), photothermal (PTT), photodynamic (PDT), sonodynamic (SDT), immune and starvation therapies (ST), emphasizing single-atom, multimetallic, biomimetic, and AI-assisted design strategies of nanozymes. Single-atom and multimetallic nanozymes offer superior catalytic precision, atom efficiency, and programmable pathways over conventional nanomaterials. While AI-assisted design accelerates discovery of optimal compositions and therapeutic environment compatibility, enabling controlled ROS generation and TME responsiveness and hence enhancing tumor selectivity and therapeutic efficacy, their combination may represent a transformative direction for precision cancer therapy. Despite encouraging progress, challenges related to in vivo specificity, long-term biosafety, scalable synthesis, and clinical translation remain. Addressing these issues through interdisciplinary innovation will be critical for advancing next-generation intelligent nanozyme platforms toward clinical oncology.